Human Gene Module / Chromosome 8 / KIF13B

KIF13BKinesin family member 13B

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 5
Rare Variants / Common Variants
9 / 0
Aliases
KIF13B, GAKIN
Associated Syndromes
-
Chromosome Band
8p12
Associated Disorders
-
Relevance to Autism

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014).

Molecular Function

The protein encoded by this gene is involved in reorganization of the cortical cytoskeleton and regulates axon formation by promoting the formation of extra axons. It may also be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to KIF13B (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Synaptic, transcriptional and chromatin genes disrupted in autism De Rubeis S , et al. (2014) Yes -
2 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
3 Primary Integrated systems analysis reveals a molecular network underlying autism spectrum disorders Li J , et al. (2015) Yes -
4 Support - Zhou X et al. (2022) Yes -
5 Support - Yasser Al-Sarraj et al. (2024) Yes -
Rare Variants   (9)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - nonsynonymous_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.2342G>A p.Arg781Gln missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.831C>T p.Asn277%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.4411G>A p.Val1471Ile missense_variant Unknown - Unknown 25549968 Li J , et al. (2015)
c.3596C>G p.Thr1199Ser missense_variant De novo - - 25363760 De Rubeis S , et al. (2014)
c.2878C>T p.Arg960Trp missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.4598C>T p.Ala1533Val missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1882C>T p.Arg628Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.3256C>T p.Arg1086Ter stop_gained De novo - Unknown 38572415 Yasser Al-Sarraj et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). De novo missense variants in this gene were also identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014); both missense variants were described as not present in dbSNP or ESP and predicted to be either probably damaging or possibly damaging by PolyPhen-2 in Sanders et al., 2015.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). De novo missense variants in this gene were also identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014); both missense variants were described as not present in dbSNP or ESP and predicted to be either probably damaging or possibly damaging by PolyPhen-2 in Sanders et al., 2015.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). De novo missense variants in this gene were also identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014); both missense variants were described as not present in dbSNP or ESP and predicted to be either probably damaging or possibly damaging by PolyPhen-2 in Sanders et al., 2015.

Reports Added
[New Scoring Scheme]
7/1/2018
icon
4

Increased from to 4

Description

This gene was originally identified as an ASD candidate gene based on its enrichment in an autism-associated protein interaction module. Sequencing of post-mortem brain tissue from 25 ASD cases resulted in the identification of significant non-synonymous variants in this gene with an expected false-positive rate at 0.1, confirming the involvement of this module with autism; this finding was further validated by exome sequencing of an independent cohort of 505 ASD cases and 491 controls (Li et al., 2014). De novo missense variants in this gene were also identified in ASD probands from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014); both missense variants were described as not present in dbSNP or ESP and predicted to be either probably damaging or possibly damaging by PolyPhen-2 in Sanders et al., 2015.

Krishnan Probability Score

Score 0.44467915612152

Ranking 15806/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.000199447010513

Ranking 12715/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.93912941080459

Ranking 14102/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score 0.32770880616958

Ranking 2323/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
Submit New Gene

Report an Error